Useful camptothecin and camptothecin-like compounds that can be produced using intermediates and processes of the present Invention include compounds described in U.S. Pat. No. 4,894,456 to Wall et al. issued Jan. 16, 1990; U.S. Pat. No. 4,399,282 to Miyasaka, et al. issued Aug. 16, 1983; U.S. Pat. No. 4,399,276 to Miyasaka, et al. issued Aug. 16, 1983; U.S. Pat. No. 4,943,579 to Vishnuvajjala, et al. issued Jul. 24, 1990; European Patent Application 0 321 122 A2 filed by SmithKline Beckman Corporation, and published Jun. 21, 1989; U.S. Pat. No. 4,473,692 to Miyasaka, et al. issued Sep. 25, 1984; European Patent application No. 0 325 247 A2 filed by Kabushiki Kaisha Yakult Honsha, and published Jul. 26, 1989; European Patent application 0 556 585 A2 filed by Takeda Chemical Industries, and published Aug. 25, 1993; U.S. Pat. No. 4,981,968 to Wall, et al. issued Jan. 1, 1991; U.S. Pat. No. 5,049,668 to Wall, et al. issued Sep. 17, 1991; U.S. Pat. No. 5,180,722 to Wall, et al. issued Jan. 19, 1993 and European Patent application 0 540 099 A1, filed by Glaxo Inc., and published May 5, 1993.
Previous methods used in the preparation of camptothecin and camptothecin-like compounds employ resolutions or chiral auxiliaries to obtain enantiomerically enriched intermediates. A problem with these methods is that a resolution necessitates discarding half of the racemic material and a chiral auxiliary requires utilizing stoichiometric amounts of a chiral subunit to enantioselectively install the chiral center.
The present Invention describes a method for producing enantiomerically enriched intermediates useful for the preparation of camptothecin and camptothecin-like compounds using a process of catalytic asymmetric induction. In this process, a chiral catalyst used in sub-stoichiometric amounts influences the stereoselective formation of the chiral center. Additionally, the process continually regenerates the chiral catalyst preventing waste.